Binuclear metal complexes with a novel hexadentate imidazole derivative for the cleavage of phosphate diesters and biomolecules: distinguishable mechanisms

Abstract

Phosphate bond cleavage is essential to physiological, antibacterial, or antitumor activity, as well as the elimination of chemical warfare agents. In this work, three transition metal binuclear complexes (Cu₂LCl₄, Co₂LCl₄, and Zn₂LCl₄) with a novel hexadentate imidazole derivative (L) were conveniently ‘one-pot’ synthesized to test their ability to cleave phosphate diesters, c-Myc oligonucleotides, and plasmid pBR322 DNA. Single crystal structures indicated that each central metal ion is penta-coordinated for each binuclear complex. Cu₂LCl₄ with a space group of P21/n is monoclinic, and Zn₂LCl₄ with a P space group is triclinic. Co₂LCl₄ with a C2/c space group is monoclinic and cis-configurational. Unfortunately, the tested complexes displayed low activity in the hydrolysis of two diesters and pBR322 plasmid DNA (although stronger ability was exhibited for c-Myc) used in this work, which is probably ascribed to the lack of bimetallic cooperation due to a relatively larger metal–metal distance in excess of 10 Å. Density function theory (DFT) calculation provides evidence for the highest activity of Co₂LCl₄ among these three complexes in the hydrolysis reaction. With respect to the oxidative cleavage, only Cu₂LCl₄ displayed catalytic activity for these substrates in this work. As compared to the hydrolytic cleavage, the Cu₂LCl₄-mediated oxidative cleavage or destruction of each substrate was more efficient, and was accompanied by an excess of six orders of magnitude (approximately 7.75 million-fold) rate acceleration in the oxidative cleavage of HPNP, probably originating from the dominant nucleophilic attack of a greater amount of reactive hydroxyl free radicals against hydroxyl anions. The HPNP oxidative cleavage produces one attractive non-lactone phosphate monoester due to the direct attack of metal-activated hydroxyl radicals.